Potassium Phosphate, Tribasic → HCID 86687621, compound

HRID 1473561Notes

Reaction equation

HRID 1473561 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]([O:28][CH3:29])=[C:6]([C:8]2[C:17]3[C:12](=[CH:13][C:14]([S:18]([NH:21][C:22]4[CH:27]=[CH:26][N:25]=[CH:24][N:23]=4)(=[O:20])=[O:19])=[CH:15][CH:16]=3)[CH:11]=[CH:10][N:9]=2)[CH:7]=1.[F:30][C:31]([F:42])([F:41])[C:32]1[CH:33]=[C:34](B(O)O)[CH:35]=[CH:36][CH:37]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>>[CH3:29][O:28][C:5]1[CH:4]=[CH:3][C:2]([C:36]2[CH:35]=[CH:34][CH:33]=[C:32]([C:31]([F:42])([F:41])[F:30])[CH:37]=2)=[CH:7][C:6]=1[C:8]1[C:17]2[C:12](=[CH:13][C:14]([S:18]([NH:21][C:22]3[CH:27]=[CH:26][N:25]=[CH:24][N:23]=3)(=[O:20])=[O:19])=[CH:15][CH:16]=2)[CH:11]=[CH:10][N:9]=1

Participants

5

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27343883-(Trifluoromethyl)phenylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 86687622HCID 86687622, compound

Product 1

HCID 86687621HCID 86687621, compoundYield 43.8%

Conditions

Temperature
120 °C

Procedure

A vial was charged with 1-(5-CHLORO-2-METHOXYPHENYL)-N-(PYRIMIDIN-4-YL)ISOQUINOLINE-6-SULFONAMIDE (Example 146; 64.66 mg, 0.151 mmol) (3-(trifluoromethyl)phenyl)boronic acid (57.5 mg, 0.303 mmol), dicyclohexyl(2′,6′-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine (3.11 mg, 7.57 mmol), chloro(2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl)[2-(2-aminoethylphenyl)]palladium(ii) dichloromethane (11.47 mg, 0.015 mmol), and potassium phosphate (96 mg, 0.454 mmol). The vial was flushed with Ar (g), then 1,4-dioxane (689 μl) and water (68.9 μl) were added in sequence. The vial was sealed and heated in a Biotage Initiator microwave reactor for 30 min at 120° C. The mixture was extracted with EtOAc (4×), and the combined organic extracts were concentrated. The residue was purified by chromatography on silica gel (12-g Redi-Sep Gold column, 3.5% MeOH/DCM) to give 1-(4-methoxy-3′-(trifluoromethyl)-[1,1′-biphenyl]-3-yl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (35.6 mg, 0.066 mmol, 43.8% yield) as a light-yellow solid. 1H NMR (400 MHz, DMSO-d6) δ=13.02 (br. s., 1H), 8.76-8.64 (m, 2H), 8.57 (s, 1H), 8.25 (d, J=5.8 Hz, 1H), 8.12 (d, J=5.7 Hz, 1H), 8.04-7.90 (m, 4H), 7.83-7.72 (m, 2H), 7.70-7.62 (m, 2H), 7.35 (d, J=8.7 Hz, 1H), 7.03 (d, J=6.0 Hz, 1H), 3.71 (s, 3H). m/z (ESI) 537.2 (M+H)+.

Workup

  1. customThe vial was flushed with Ar (g)
  2. addition1,4-dioxane (689 μl) and water (68.9 μl) were added in sequence
  3. customThe vial was sealed
  4. extractionThe mixture was extracted with EtOAc (4×)
  5. concentrationthe combined organic extracts were concentrated
  6. customThe residue was purified by chromatography on silica gel (12-g Redi-Sep Gold column, 3.5% MeOH/DCM)

Sources & evidence

ORD record
ord-83d50d37a04d4670891770e247968d7c
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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